Decay-accelerating factor expression on either effector or target cells inhibits cytotoxicity by human natural killer cells.

Decay-accelerating factor expression on either effector or target cells inhibits cytotoxicity by human natural killer cells.
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DOI:
10.4049/jimmunol.149.6.2055
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发表时间:
1992-09
影响因子:
4.4
通讯作者:
R. Finberg;W. White;A. Nicholson‐Weller
R. Finberg;W. White;A. Nicholson‐Weller
中科院分区:
医学2区
文献类型:
--
作者:
R. Finberg;W. White;A. Nicholson‐Weller

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先前的研究表明,新鲜分离的CD 16 + NK细胞缺乏衰变加速因子(decay-accelerating factor,CD 55)的表达,CD 55是C3激活的膜调节因子。在这项研究中,我们调查的意义,NK细胞介导的溶解,靶细胞和效应细胞上的CD 45表达。通过几种方法研究了IFN-γ表达对NK细胞靶标敏感性的影响:首先,从K562克隆IFN-γ细胞系;第二,用外源性纯化IFN-γ重建克隆的IFN-γ细胞;第三,使用抗IFN-γ F(ab ')2阻断IFN-γ + K562细胞上的IFN-γ功能。一致地,靶细胞膜中天然存在的或实验掺入的β-内酰胺酶的存在提供了靶细胞针对裂解的保护,并且这种保护可以用抗β-内酰胺酶阻断。类似地,与在其膜中没有掺入外源性β-内酰胺酶的相同靶细胞相比,在其质膜中掺入外源性β-内酰胺酶的抗体依赖性细胞介导的细胞毒性的靶细胞对NK细胞的抗体依赖性细胞介导的细胞毒性变得不那么敏感。掺入效应NK细胞质膜中的β-内酰胺酶使NK细胞在杀死K562靶点方面不那么有效。已知NK细胞的功能是调节C3活化,我们能够证明分离的NK细胞能够释放C3。也有可能是,参与NK细胞功能的NK细胞代表了一个新的,非补体依赖性功能的NK细胞。
Previous studies have shown that freshly isolated CD16+ NK cells are deficient in the expression of decay-accelerating factor (DAF), or CD55, a membrane regulator of C3 activation. In this study we investigated the significance, for NK cell-mediated lysis, of DAF expression on the target and effector cells. The effect of DAF expression on the susceptibility of NK cell targets was investigated by several means: first, DAF- cell lines were cloned from K562; second, the cloned DAF- cells were reconstituted with exogenous purified DAF; and third, anti-DAF F(ab')2 was used to block DAF function on the DAF+ K562 cells. Consistently, the presence of DAF in the target cell membrane, either naturally occurring or experimentally incorporated, afforded the target cell protection against lysis, and this protection could be blocked with anti-DAF. Similarly, targets for antibody-dependent cell-mediated cytotoxicity with exogenous DAF incorporated in their plasma membrane became less sensitive to antibody-dependent cell-mediated cytotoxicity by NK cells compared with the same target cells without incorporated DAF in their membranes. DAF incorporated in the plasma membranes of the effector NK cells made the NK cells less effective at killing K562 targets. The known function of DAF is to regulate C3 activation, and we were able to demonstrate that the isolated NK cell is capable of releasing C3. It is also possible that the participation of DAF in NK cell function represents a new, noncomplement-dependent function for DAF.